It is the long-range purpose of this project to study how various chemicals and physiological changes affect xenobiotic metabolism by the body. This laboratory has concentrated its effort on the lung as a target organ for exposure to environmental stresses. Present studies include isolation of rabbit lung cell types for the purpose of studying localization of xenobiotic metabolism within the lung and toxication-detoxication mechanisms in individual cell populations. The following model enzyme systems are being used for study of individual xenobiotic metabolic pathways in lung cell populations: coumarin hydroxylase, 7-ethoxycoumarin deethylase, benzo(a)pyrene hydroxylase, and N-N-dimethylaniline N-oxidase. Different lung cell fractions (mixed cell populations) appear to have different metabolic profiles indicating possible differences in cytochrome content in the cell types. Mixed-function oxidase activity is now being studied and compared in cell fractions containing either 80% alveolar type II cells or 70% nonciliated bronchiolar epithelial cells (Clara cells).